WO2013125688A1 - Composé 9-azanoradamantane n-oxyle et son procédé de production et catalyseur d'oxydation organique et procédé d'oxydation d'alcools utilisant un composé 9-azanoradamantane n-oxyle - Google Patents

Composé 9-azanoradamantane n-oxyle et son procédé de production et catalyseur d'oxydation organique et procédé d'oxydation d'alcools utilisant un composé 9-azanoradamantane n-oxyle Download PDF

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WO2013125688A1
WO2013125688A1 PCT/JP2013/054554 JP2013054554W WO2013125688A1 WO 2013125688 A1 WO2013125688 A1 WO 2013125688A1 JP 2013054554 W JP2013054554 W JP 2013054554W WO 2013125688 A1 WO2013125688 A1 WO 2013125688A1
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group
optionally substituted
alkyl
azanoradamantane
cycloalkyl
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Japanese (ja)
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好治 岩渕
正俊 澁谷
龍輔 土井
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国立大学法人東北大学
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Priority to US14/380,794 priority Critical patent/US9114390B2/en
Priority to JP2014500954A priority patent/JP6225103B2/ja
Publication of WO2013125688A1 publication Critical patent/WO2013125688A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/006—Catalysts comprising hydrides, coordination complexes or organic compounds comprising organic radicals, e.g. TEMPO
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2265—Carbenes or carbynes, i.e.(image)
    • B01J31/2269—Heterocyclic carbenes
    • B01J31/2273—Heterocyclic carbenes with only nitrogen as heteroatomic ring members, e.g. 1,3-diarylimidazoline-2-ylidenes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2265—Carbenes or carbynes, i.e.(image)
    • B01J31/2278—Complexes comprising two carbene ligands differing from each other, e.g. Grubbs second generation catalysts
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B63/00—Purification; Separation; Stabilisation; Use of additives
    • C07B63/04—Use of additives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/22—Bridged ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/14—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/70—Oxidation reactions, e.g. epoxidation, (di)hydroxylation, dehydrogenation and analogues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2527/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
    • C07C2527/24—Nitrogen compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/52—Ortho- or ortho- and peri-condensed systems containing five condensed rings

Definitions

  • the present invention relates to a 9-azanoradamantane N-oxyl compound, an organic molecular oxidation catalyst containing 9-azanoradamantane N-oxyl compound, a method for producing 9-azanoradamantane N-oxyl compound, and the 9-azane
  • the present invention relates to an alcohol oxidation method for selectively oxidizing a primary alcohol using a noradamantane N-oxyl compound.
  • the oxidation reaction of alcohol to a carbonyl compound is one of the most basic reactions used in organic synthesis of high value-added compounds such as pharmaceuticals, agricultural chemicals, fragrances and chemical products. Therefore, many methods have been developed since ancient times. However, most of them are a method using an oxidizing agent having toxicity and explosive properties, and a method requiring an extremely low temperature of ⁇ 40 ° C. or less. In such a background, 2,2,6,6-tetramethylpiperidine 1-oxyl (2,2,6,6-tetramethylpiperidine 1-oxyl, hereinafter sometimes referred to as “TEMPO”) is various. Since an alcohol is oxidized under an extremely mild condition of 0 ° C.
  • Non-patent Document 1 inexpensive and environmentally friendly sodium hypochlorite aqueous solution
  • Non-patent Document 2 inexpensive and environmentally friendly sodium hypochlorite aqueous solution
  • oxidizing agents such as iodobenzene diacetate (PhI (OAc) 2 )
  • Non-patent Document 3 iodobenzene diacetate
  • a nitroxyl radical having an azaadamantane skeleton (2-azaadamantane N-oxyl (hereinafter sometimes referred to as “AZADO”) and 1-methyl-2-azaadamantane N-oxyl (hereinafter referred to as “AZADO”) “1-Me-AZADO”)
  • AZADO 1-methyl-2-azaadamantane N-oxyl
  • aza It has a noradamantane skeleton (9-azanoradamantane N-oxyl, hereinafter sometimes referred to as “Nor-AZADO”), has higher catalytic activity than TEMPO, and bulky in which oxidation does not proceed in TEMPO Oxidation of secondary alcohol (Non-Patent Documents 4, 5, 6, 7, 8 and Patent Documents 1, 2, 3, 4, 5).
  • Non-patent Document 9 a reaction that selectively oxidizes primary alcohol proceeds in a substrate in which primary alcohol and secondary alcohol coexist.
  • a method of selectively oxidizing a specific alcohol is important as another functional group differentiation method in the synthesis of a polyfunctional compound that is usually differentiated and synthesized by a protecting group. Compared to the use of protecting groups that require steps of protection and deprotection, it can be said that this reaction is an important reaction that contributes to the shortening of the synthesis process in that it can be distinguished in one step of the alcohol oxidation reaction. Therefore, many examples of natural product synthesis utilizing this reaction have been reported.
  • the present inventors have an azanoradamantane skeleton and at least 1 in the 1,5 position.
  • the present invention was completed by finding that a 9-azanoradamantane N-oxyl compound in which two alkyl groups are substituted and the nitrogen atom is oxygenated exhibits high catalytic activity in alcohol oxidation.
  • the present invention relates to a 9-azanoradamantane N-oxyl compound and a method for producing the same, an organic molecular oxidation catalyst using the 9-azanoradamantane N-oxyl compound, and a method for oxidizing alcohols as described below.
  • R 1 and R 2 represent a hydrogen atom or an alkyl group. However, when one of R 1 and R 2 is hydrogen, the other is an alkyl group.
  • An organic molecular oxidation catalyst comprising the 9-azanoradamantane N-oxyl compound described in (1) above.
  • Formula (2) (In the above formula, R 1 and R 2 are as defined above.) A method for producing a 9-azanoradamantane N-oxyl compound represented by the above formula (1), wherein the method comprises at least a step of oxidizing the azanoradamantane compound represented by formula (1).
  • Formula (3) (In the above formula, R 1 and R 2 are as defined above.
  • R 3 is a hydrogen atom, a halogen atom, a nitro group, a cyano group, a hydroxy group, a mercapto group, an amino group, a formyl group, a carboxyl group, a sulfo group.
  • Ra is halogen, C 1-6 alkyl group, C 1-6 haloalkyl group, C 3-6 cycloalkyl group, C 1-6 alkoxy group, C 1-6 alkoxy C 1-6 alkyl group, C 1-6 alkylsulfenyl C 1-6 alkyl group, C 1-6 haloalkoxy group, C 1-6 alkylsulfenyl group, C 1-6 alkylsulfinyl group, C 1-6 alkylsulfonyl group, C 1-6 haloalkylsulfenyl Group, C 1-6 haloalkylsulfinyl group, C 1-6 haloalkylsulfonyl group, C 2-6 alkenyl group, C 2-6 haloalkenyl group, C 2-6 alkenyloxy group, C 2-6 haloalkenyloxy group, C 2-6 alkeny
  • X represents a hydrogen atom or a group selected from an acyl group, a carbamoyl group, a sulfonamide group, an alkyl group, an allyl group, a benzyl group, an aryl group, a silyl group, a hydroxyl group, an alkoxy group, and an oxygen atom.
  • a process for producing a 9-azanoradamantane N-oxyl compound represented by the above formula (1) A process for producing a 9-azanoradamantane N-oxyl compound represented by the above formula (1).
  • a ketobicycloamine compound was synthesized by condensation of 2,6-heptanedione obtained by methylation with ammonium chloride and acetone dicarboxylic acid, and then condensed with hydrazine.
  • a method for oxidizing alcohols comprising oxidizing an alcohol in the presence of the 9-azanoradamantane N-oxyl compound according to (1) to synthesize a corresponding oxo compound.
  • the alcohol is a compound having a primary alcohol and / or a secondary alcohol.
  • the alcohol is a compound having a primary alcohol and a secondary alcohol, and the primary alcohol is selectively oxidized.
  • a nitroxyl radical having an azanoradamantane skeleton and substituted with at least one alkyl group at positions 1, 5 as an oxidation catalyst
  • primary alcohol selective oxidation reaction can be carried out efficiently with a small amount of catalyst and a short reaction time.
  • Primary alcohols can be oxidized with higher selectivity than AZADO and 1-Me-AZADO.
  • “selectively oxidize primary alcohol”, “primary alcohol selective oxidation reaction”, “primary alcohol selective oxidation catalyst”, “primary alcohol selectivity”, etc. in the present invention synonymously means a reaction, function or catalyst capable of obtaining 50% or more of a reaction product in which only a primary alcohol is oxidized in an oxidation reaction of a substrate in which a primary alcohol and a secondary alcohol coexist.
  • it means a reaction, function or catalyst capable of obtaining 70% or more of a reaction product in which only a primary alcohol is oxidized.
  • it means a reaction, function or catalyst capable of obtaining a reaction product in which only a primary alcohol is oxidized by 90% or more.
  • the present invention is characterized in that a 9-azanoradamantane N-oxyl compound represented by the following formula (1) is used as an organic molecular oxidation catalyst.
  • R 1 and R 2 represent a hydrogen atom or an alkyl group. However, when one of R 1 and R 2 is hydrogen, the other is an alkyl group.
  • the alkyl group represented by R 1 and R 2 in the formula (1) is not particularly limited as long as it is known in the art and can achieve the intended purpose. Is mentioned.
  • Examples of the lower alkyl group include C 1-5 alkyl groups, specifically, methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, i-butyl group, sec-butyl group, Examples thereof include a t-butyl group and a pentyl group, and a methyl group is particularly preferable.
  • R 1 and R 2 are as defined above. It can synthesize
  • the azanoradamantane compound represented by the above formula (2) is represented by the following formula (3)
  • R 1 and R 2 are as defined above.
  • R 3 is a hydrogen atom, a halogen atom, a nitro group, a cyano group, a hydroxy group, a mercapto group, an amino group, a formyl group, a carboxyl group, a sulfo group.
  • Ra is halogen, C 1-6 alkyl group, C 1-6 haloalkyl group, C 3-6 cycloalkyl group, C 1-6 alkoxy group, C 1-6 alkoxy C 1-6 alkyl group, C 1-6 alkylsulfenyl C 1-6 alkyl group, C 1-6 haloalkoxy group, C 1-6 alkylsulfenyl group, C 1-6 alkylsulfinyl group, C 1-6 alkylsulfonyl group, C 1-6 haloalkylsulfenyl Group, C 1-6 haloalkylsulfinyl group, C 1-6 haloalkylsulfonyl group, C 2-6 alkenyl group, C 2-6 haloalkenyl group, C 2-6 alkenyloxy group, C 2-6 haloalkenyloxy group, C 2-6 alkeny
  • X represents a hydrogen atom or a group selected from an acyl group, a carbamoyl group, a sulfonamide group, an alkyl group, an allyl group, a benzyl group, an aryl group, a silyl group, a hydroxyl group, an alkoxy group, and an oxygen atom.
  • It can be synthesized by closing a hydrazonoazabicyclo [3.3.1] nonane compound represented by the following formula to form an azanoradamantane ring.
  • X may be other than the groups exemplified above as long as it does not adversely affect the reaction of closing the hydrazono [3.3.1] nonane compound to form an azanoradamantane ring.
  • Examples of the acyl group of X include C 1-10 acyl groups such as formyl group, acetyl group, propanoyl group, bivaloyl group, and benzoyl group.
  • Examples of the carbamoyl group include C 1-10 carbamoyl groups such as a methoxycarbonyl group, an ethoxycarbonyl group, a tert-butoxycarbonyl group, and a benzyloxycarbonyl group.
  • Examples of the sulfonamide group include sulfonamide groups such as a methanesulfonamide group, a trifluoromethanesulfonamide group, an ethanesulfonamide group, a toluenesulfonamide group, and a nitrotoluenesulfonamide group.
  • Examples of the aryl group include C 6-18 aryl groups such as a phenyl group, a tolyl group, and a xylyl group.
  • silyl group examples include silyl groups substituted with three alkyl groups such as a trimethylsilyl group, a triethylsilyl group, a triisopropylsilyl group, and a Tert-butyldimethylsilyl group.
  • alkoxy group examples include C 1-10 alkoxy groups such as a methoxy group, an ethoxy group, and a propoxy group.
  • the alkyl group is the same as R 1 above.
  • the compound represented by the above formula (3) is represented by the following formula (4).
  • R 1 , R 2 and X are as defined above. It can be synthesized by condensing a ketoazabicyclo [3.3.1] nonane compound represented by the formula with phenylhydrazine.
  • the compound represented by the above formula (4) can be synthesized by condensing 2,6-heptanedione obtained by methylation after converting glutaryl chloride to diwine levamide, ammonium chloride, and acetone dicarboxylic acid. .
  • the synthesis method exemplified above is merely an example for synthesizing the compound represented by the formula (1), and may be another method.
  • the compounds represented by the above formulas (1) to (4) include derivatives in which substituents such as alkyl groups, halogen atoms, and alkoxy groups are substituted in addition to positions 1 and 5 of the azanoradamantane nucleus. It is.
  • the “alcohol” that is an oxide may be a primary alcohol represented by the following general formula (5) or a secondary alcohol represented by the following general formula (6).
  • the substituents X and Y in the general formulas (5) and (6) are not particularly limited as long as they do not adversely affect the oxidation reaction.
  • X and Y may be a linear or branched alkyl group that may be substituted, a cyclic alkyl group that may be substituted, an aromatic hydrocarbon group that may be substituted, or a substituted group.
  • Aromatic heterocyclic groups can be mentioned. Also included are compounds having a plurality of structural units represented by the general formulas (5) and (6) in the same molecule.
  • Examples of the linear or branched alkyl group in the “optionally substituted linear or branched alkyl group” for X and Y include an alkyl group having about 1 to 16 carbon atoms. be able to. Among these, an alkyl group having about 1 to 8 carbon atoms can be suitably applied.
  • alkyl group examples include a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, tert-butyl group, n-pentyl group, isopentyl group, 2-methylbutyl group, neopentyl group, 1-ethylpropyl group, n-hexyl group, isohexyl group, 4-methylpentyl group, 3-methylpentyl group, 2-methylpentyl group, 1-methylpentyl group, 3,3- Dimethylbutyl group, 2,2-dimethylbutyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 2-ethylbutyl group, heptyl 1-methylhexyl group, 2-methylhexyl group, 3-
  • Examples of the cyclic alkyl group include cycloalkyl having about 3 to 7 carbon atoms, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cycloheptyl group.
  • the aromatic ring constituting the aromatic ring hydrocarbon group may be either a monocyclic aromatic hydrocarbon ring or a condensed polycyclic aromatic hydrocarbon ring.
  • the aromatic hydrocarbon group include aryl groups having about 6 to 14 carbon atoms such as phenyl group, naphthyl group, anthryl group, azulenyl group, phenanthryl group, and acenaphthylenyl.
  • heterocyclic ring constituting the aromatic heterocyclic group examples include a 5-membered or 6-membered monocyclic heterocyclic ring, or a 6-membered + 5-membered or 6-membered + 6-membered condensed heterocyclic ring. It is not limited to.
  • examples of the ring-forming hetero atom constituting the heterocyclic ring include, but are not limited to, 1 to 3 atoms selected from an oxygen atom, a sulfur atom, and a nitrogen atom.
  • the heterocyclic ring is preferably an aromatic ring, but may be saturated or partially saturated. When the heterocycle is saturated or partially saturated, the heteroatom moiety is often preferably protected by a suitable protecting group, but may be left as is.
  • aromatic heterocyclic groups include furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2, 4-oxadiazolyl group, 1,3,4-oxadiazolyl group, furazanyl group, 1,2,3-thiadiazolyl group, 1,2,4-thiadiazolyl group, 1,3,4-thiadiazolyl group, 1,2,3- A monocyclic aromatic heterocyclic group such as triazolyl group, 1,2,4-triazolyl group, tetrazolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group or triazinyl, or benzofuranyl group, isobenzofuranyl group, Benzo [b] thienyl group, indolyl group, iso
  • Examples of the substituent that can be present on a linear or branched alkyl group, cyclic alkyl group, aromatic hydrocarbon group, or aromatic heterocyclic group include a methyl group, an ethyl group, and a propyl group.
  • An alkenyl group having about 2 to 6 carbon atoms such as a group or allyl, an alkynyl group having about 2 to 6 carbon atoms such as an ethynyl group or propargyl, a hydroxyl group, an optionally substituted amino group, and an optionally substituted sulfonyl group , Optionally substituted sulfonamido group, cyano group, nitro group, nitroso group, optionally substituted amidino group, carboxy group An alkoxycarbonyl group having about 2 to 7 carbon atoms, an optionally substituted carbamoyl group,
  • the type of protecting group is not particularly limited, and suitable protecting groups for hydroxyl groups and amino groups include, for example, Green et al., Protective Groups in Organic Synthesis, 3rd Edition, 1999, John Wiley & Sons, Inc.
  • the product can be appropriately selected with reference to a book such as, and can be removed from the product aldehyde or ketone compound by an appropriate means after alcohol oxidation.
  • co-oxidant also referred to as “reoxidant” or “bulk oxidant” in the present invention is a source of oxidizing ability to the catalyst, and hydroxylamine is converted into a nitroxyl radical or oxoammonium salt. Or there is no restriction
  • co-oxidants include peroxyacids, hydrogen peroxide, hypohalous acid and salts thereof, perhalogenates and salts thereof, persulfates, halides, halogenated N-bromosuccinimides, and the like.
  • the oxidation reaction in the present invention can be performed in a solvent or without a solvent.
  • a solvent there is no particular limitation as long as it does not inhibit the reaction.
  • solvents include, for example, aliphatic hydrocarbons such as hexane, heptane, or petroleum ether, aromatic hydrocarbons such as benzene, toluene, xylene, nitriles such as acetonitrile and propionitrile.
  • Halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane, carbon tetrachloride, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether, formamide, dimethylformamide, Amides such as dimethylacetamide, hexamethylphosphoric triamide, sulfoxides such as dimethyl sulfoxide, esters such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate, diethyl carbonate Carboxylic acids such as acetic acid, formic acid and propionic acid, fluorinated alcohols such as trifluoroethanol and hexafluoroisopropanol, tertiary alcohols such as tert-butyl alcohol, sulfolane and water, These may also be used
  • aliphatic hydrocarbons preferred are aliphatic hydrocarbons, aromatic hydrocarbons, nitriles, halogenated hydrocarbons, esters, carboxylic acids, water or mixtures thereof. More preferred are dichloromethane, acetonitrile, acetic acid, toluene, ethyl acetate, isopropyl acetate, water or a mixture thereof, and particularly preferred are dichloromethane, acetonitrile, acetic acid, dichloromethane-water mixed solution, acetonitrile-water mixed solution, toluene. -Water mixed solution, ethyl acetate-water mixed solution and the like.
  • a buffering agent such as an inorganic salt or an organic salt can be appropriately added to the reaction mixture, and examples of the buffering agent include alkali metal or alkaline earth metal carbonate, alkali metal or alkaline earth metal bicarbonate. Salt, alkali metal or alkaline earth metal hydroxide, alkali metal or alkaline earth metal phosphate, alkali metal or alkaline earth metal acetate, etc., preferably sodium bicarbonate, Examples thereof include sodium carbonate, sodium acetate, and phosphate.
  • an additive for promoting the reaction can be added as appropriate.
  • an additive for example, when sodium hypochlorite is used as a co-oxidant, quaternary ammonium salts, alkali metal halides and the like can be mentioned, and preferably tetrabutylammonium chloride, tetrabutyl bromide. Ammonium, sodium bromide, potassium bromide or a mixture thereof.
  • oxygen when used as a co-oxidant, it can be selected from additives generally used in an air oxidation reaction using TEMPO, such as nitrite, nitrite, inorganic acid, organic acid, bromine, Or transition metals such as copper, iron and ruthenium, preferably a mixture of sodium nitrite and acetic acid, a mixture of sodium nitrite and bromine, a mixture of sodium nitrite and iron chloride, copper chloride, tert-butyl nitrite, etc. Can be mentioned.
  • additives generally used in an air oxidation reaction using TEMPO such as nitrite, nitrite, inorganic acid, organic acid, bromine, Or transition metals such as copper, iron and ruthenium, preferably a mixture of sodium nitrite and acetic acid, a mixture of sodium nitrite and bromine, a mixture of sodium nitrite and iron chloride, copper chloride, tert-butyl nitrite, etc.
  • the amount of compound (I) used with respect to the alcohols is not particularly limited, but is usually 0.0001 mol% to 1000 mol% with respect to the alcohols (0.0001% to 1000% of the number of moles of the raw alcohol). 0.0001 mol% to 150 mol% is preferable, and 0.001 mol% to 50 mol% is more preferable. It is especially preferable to set it as 0.1 mol% to 20 mol%.
  • the reaction temperature varies depending on the amount of the raw material compound, bulk oxidant and reagent, but is usually ⁇ 80 ° C. to 120 ° C., preferably 0 to 40 ° C.
  • the target oxidation product can be isolated by a usual post-treatment and then by an isolation operation such as extraction, recrystallization or column chromatography.
  • the oxidation reaction catalyzed by the nitroxyl radical represented by (1) according to the present invention is considered to proceed by a reaction mechanism similar to that generally considered in the oxidation reaction catalyzed by TEMPO or AZADO. Therefore, it is considered that the hydroxylamine compound corresponding to the nitroxyl radical represented by (1) and the oxoammonium salt also show the same catalytic activity as the nitroxyl radical compound.
  • N, O-dimethylhydroxylamine hydrochloride (42 g, 431 mmol) was added to a solution of glutaryl chloride (25 ml, 196 mmol) in dichloromethane (500 ml) at room temperature, and then pyridine (95 ml, 1.18 mol) was added under ice cooling. It was dripped. After stirring at room temperature for 2 hours, the reaction mixture was filtered through celite. The filtrate was concentrated under reduced pressure, diethyl ether (300 ml) was added, and celite filtration was performed again, followed by concentration under reduced pressure to obtain a diwine levamide body.
  • urea / hydrogen peroxide (urea peroxide or UHP (urea hydrogen peroxide)) was added, and the mixture was stirred at room temperature for 40 minutes. Saturated multistory water was added and extracted with diethyl ether. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 1,5-dimethyl-9-azanoradamantane N-oxyl (DMN-AZADO) (69 mg, 28%).
  • DN-AZADO 1,5-dimethyl-9-azanoradamantane N-oxyl
  • DMN-AZADO IR (neat, cm ⁇ 1 ): 2955, 2869, 1732, 1456, 1374, 1337; MS m / z 166 (M + ), 93 (100%); HRMS (EI): calcd for C 10 H 16 NO ⁇ 1666.132 (M + ), found 166.1232; Anal: calcd for C 10 H 16 NO ⁇ : C, 72.25; H, 9.70; N, 8.43, found: C, 71.91; H, 9.61; N, 8.07.
  • the catalytic activity in the primary alcohol selective oxidation reaction between DMN-AZADO synthesized by the above method and the existing nitroxyl radical type oxidation catalysts TEMPO and 1-Me-AZADO was compared. First, the reaction was carried out under conditions using sodium hypochlorite as a cooxidant.
  • TEMPO When 1.5 equivalents of sodium hypochlorite is used, TEMPO recovers 17% of unreacted raw material, and when 1-Me-AZADO is used, 24% of primary alcohol and secondary alcohol. A diketone body in which both were oxidized was obtained. Therefore, when TEMPO and 1-Me-AZADO are used as catalysts, the yield is moderate, whereas when DMN-AZADO is used, the target hydroxy is as high as 94%. A ketone body was obtained. As a result, it was revealed that DMN-AZADO functions as a catalyst for alcohol oxidation reaction, and has both primary alcohol selectivity and high reactivity.
  • DMN-AZADO functions as a catalyst for alcohol oxidation reaction, and is a catalyst having both primary alcohol selectivity and high reactivity in a short time compared to TEMPO regardless of the type of substrate. It became.
  • Oleano-12-ene-11-oxo-3 ⁇ , 30-diol (41.2 mg, 0.090 mmol) was oxidized by the same method as described in Example 2-1, and the target compound (37.3 mg, 91 %).
  • the catalytic activity was compared using DMN-AZADO, TEMPO, 1-Me-AZADO, and AZADO under conditions using natural product betulin as a substrate and diacetoxyiodobenzene as a cooxidant.
  • DMP Dess-Martin periodinane
  • DMN-AZADO has a higher reactivity than TEMPO even under conditions where diacetoxyiodobenzene is used as a co-oxidant, and a higher primary alcohol selectivity than AZADO and 1-Me-AZADO is evident. It became.
  • DMN-AZADO can reduce the amount of the catalyst to 3 mol%.
  • the reaction proceeded with good yield.
  • the reaction time was significantly shorter for DMN-AZADO than for TEMPO.
  • the superiority of DMN-AZADO was clear compared to TEMPO in both catalyst amount and reaction time.
  • DMN-AZADO advanced the primary alcohol selective oxidation reaction in a shorter time and with higher yield than TEMPO.
  • the oxidation of the primary alcohol located in the neopentyl position also proceeds rapidly in DMN-AZADO, and it is clear that DMN-AZADO is a highly active primary alcohol selective oxidation catalyst.
  • Octadecane-1,12-diol (51.7 mg, 0.180 mmol) was oxidized by the same method as described in Example 6-1 to obtain the target compound (40.2 mg, 79%).
  • Betulin (50.4 mg, 0.114 mmol) was oxidized by the same method as described in Example 6-1 to obtain the target compound (46.0 mg, 92%).
  • Oleano-12-ene-11-oxo-3 ⁇ , 30-diol (43.4 mg, 0.095 mmol) was oxidized by a method similar to that described in Example 6-1 to give the target compound (42.8 mg, 99 %).
  • Erythrodiol (44.0 mg, 0.099 mmol) was oxidized by the same method as described in Example 6-1 to obtain the target compound (41.7 mg, 95%).
  • Isopropyl 2,3-deoxy- ⁇ -D-glucopyranoside (50.0 mg, 0.263 mmol) was oxidized by the same method as described in Example 7-1, and the target compound was converted to the methyl ester form (55.6 mg, 97%).
  • Example 7-3 Oxidation of 2,2,4-trimethylpentane-1,3-diol 2,2,4-Trimethylpentane-1,3-diol (44.4 mg, 0.304 mmol) was oxidized by a method similar to that described in Example 7-1 to give the target compound as methyl ester (48.7 mg 92%).
  • Methyl 2,3-bis-O- (phenylmethyl) - ⁇ -D-glucopyranoside (41.8 mg, 0.112 mmol) was oxidized by the same method as described in Example 7-1, and the target compound was methylated. Obtained as the ester (42.3 mg, 94%).
  • Methyl 2-On-butyl- ⁇ -D-ribofuranoside (41.5 mg, 0.188 mmol) was oxidized by the same method as described in Example 7-1, and the target compound was methyl ester (38.8 mg). 83%).
  • DMN-AZADO was shown to be able to significantly shorten the reaction time compared to TEMPO.
  • DMN-AZADO was shown to be able to significantly shorten the reaction time compared to TEMPO.
  • the present invention provides an oxidation catalyst that is more active than TEMPO, which is an existing oxidation catalyst, and is more selective than AZADO and 1-Me-AZADO in a primary alcohol selective oxidation reaction.
  • DMN-AZADO can be applied to a primary alcohol selective oxidation reaction that contributes to shortening the process of synthesizing high value-added organic compounds such as pharmaceuticals, pharmaceutical raw materials, agricultural chemicals, cosmetics, and organic materials.

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  • Inorganic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract

L'invention concerne un organocatalyseur permettant d'oxyder des alcools ; un alcool primaire est oxydé de manière sélective dans un substrat de polyol ayant plusieurs alcools dans des conditions respectueuses de l'environnement. Le catalyseur d'oxydation organique pour oxyder des alcools comporte un atome d'oxygène lié à un atome d'azote d'un squelette azanoradamantane et au moins un groupe alkyle au niveau des positions 1 et 5. L'invention concerne un catalyseur d'oxydation ayant une activité plus élevée que TEMPO, un catalyseur d'oxydation existant, au niveau de sa réaction d'oxydation sélective d'alcools primaires, et une meilleure sélectivité que AZADO et 1-Me-AZADO. Ce DMN-AZADO peut être appliqué à la réaction d'oxydation sélective d'alcools primaires qui contribue à raccourcir le procédé de synthèse pour des produits pharmaceutiques, des matériaux bruts pharmaceutiques, des produits chimiques agricoles, des produits cosmétiques, des matériaux organiques, et d'autres composés organiques à haute valeur ajoutée.
PCT/JP2013/054554 2012-02-24 2013-02-22 Composé 9-azanoradamantane n-oxyle et son procédé de production et catalyseur d'oxydation organique et procédé d'oxydation d'alcools utilisant un composé 9-azanoradamantane n-oxyle WO2013125688A1 (fr)

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JP2014500954A JP6225103B2 (ja) 2012-02-24 2013-02-22 ９−アザノルアダマンタンｎ−オキシル化合物及びその製造方法、並びに９−アザノルアダマンタンｎ−オキシル化合物を用いた有機分子酸化触媒及びアルコール類の酸化方法

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JP2019102420A (ja) * 2017-11-30 2019-06-24 パナソニックＩｐマネジメント株式会社 リチウム空気電池
WO2020032167A1 (fr) 2018-08-09 2020-02-13 三菱ケミカル株式会社 Composition pour support d'enregistrement d'hologramme, et support d'enregistrement d'hologramme
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CN115093549A (zh) * 2022-08-04 2022-09-23 浙江吉泰新材料股份有限公司 一种侧链含有abno的聚噻吩及其制备方法和应用

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JP2019102420A (ja) * 2017-11-30 2019-06-24 パナソニックＩｐマネジメント株式会社 リチウム空気電池
JP7008196B2 (ja) 2017-11-30 2022-01-25 パナソニックＩｐマネジメント株式会社 リチウム空気電池
WO2020032167A1 (fr) 2018-08-09 2020-02-13 三菱ケミカル株式会社 Composition pour support d'enregistrement d'hologramme, et support d'enregistrement d'hologramme
KR20210013114A (ko) 2018-08-09 2021-02-03 미쯔비시 케미컬 주식회사 홀로그램 기록 매체용 조성물 및 홀로그램 기록 매체
CN109499609A (zh) * 2018-12-05 2019-03-22 浙江工业大学 一种sba-15固载2-氮杂金刚烷氮氧自由基催化剂及其制备和应用
CN109499609B (zh) * 2018-12-05 2021-06-15 浙江工业大学 一种sba-15固载2-氮杂金刚烷氮氧自由基催化剂及其制备和应用
JP2020200287A (ja) * 2019-06-12 2020-12-17 株式会社トクヤマ カルボニル化合物の製造方法

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